A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens

作者:Moore Gregory L*; Bautista Cristina; Pong Erik; Nguyen Duc Hanh T; Jacinto Jonathan; Eivazi Araz; Muchhal Umesh S; Karki Sher; Chu Seung Y; Lazar Greg A
来源:mAbs, 2011, 3(6): 546-557.
DOI:10.4161/mabs.3.6.18123

摘要

Bispecific antibodies based on full-length antibody structures are more optimal than fragment-based formats because they benefit from the favorable properties of the Fc region. However, the homodimeric nature of Fc effectively imposes bivalent binding on all current full-length bispecific antibodies, an attribute that can result in nonspecific activation of cross-linked receptors. We engineered a novel bispecific format, referred to as mAb-Fv, that utilizes a heterodimeric Fc region to enable monovalent co-engagement of a second target antigen in a full-length context. mAb-Fv constructs co-targeting CD16 and CD3 were expressed and purified as heterodimeric species, bound selectively to their co-target antigens and mediated potent cytotoxic activity by NK cells and T cells, respectively. The capacity to co-engage distinct target antigens simultaneously with different valencies is an improved feature for bispecific antibodies with promising therapeutic implications.

  • 出版日期2011-12